What is the recommended treatment for a patient experiencing a scleroderma-associated interstitial lung disease (ILD) flare?

Treatment of Scleroderma-Associated ILD Flare

For a scleroderma-ILD flare, glucocorticoids may be used short-term as a bridge to definitive therapy change, but long-term glucocorticoids should be strongly avoided due to the risk of scleroderma renal crisis. 1, 2

Acute Flare Management

Short-Term Glucocorticoid Use

• Glucocorticoids have a limited role only as a bridge therapy while transitioning to more definitive immunosuppressive treatment during an acute flare 1
• For rapidly progressive SSc-ILD with acute respiratory deterioration, pulse IV methylprednisolone (1000 mg daily for 3 days) may be considered, followed by moderate-dose oral prednisone (up to 60 mg daily) with rapid taper over weeks 2
• The ACR/CHEST strongly recommends against long-term glucocorticoids (>3-6 months) in SSc-ILD due to moderate-certainty evidence of scleroderma renal crisis risk, particularly at prednisone doses >15 mg daily 1, 2, 3

Definitive Therapy Escalation

When a patient experiences disease progression or flare despite first-line treatment, the following options are recommended:

Primary Second-Line Options:

• Switch to mycophenolate if not already on it—this is the preferred second-line agent based on trials in SSc-ILD and concerns about cyclophosphamide toxicity 1
• Add or switch to rituximab, which has indirect evidence from four trials showing FVC stabilization or improvement in SSc-ILD; some experts add rituximab to mycophenolate while others switch entirely depending on risk factors 1
• Cyclophosphamide remains an option with indirect evidence from five trials showing FVC stabilization, though it is typically second-line due to its side effect profile 1
• Add nintedanib, particularly for progressive fibrosing disease on HRCT, though it only slows FVC decline and has frequent GI side effects 1, 3

Additional Considerations:

• Tocilizumab (162 mg subcutaneously weekly) is conditionally recommended for SSc-ILD progression, though it was primarily studied in early SSc-ILD 1
• Pirfenidone is NOT recommended for SSc-ILD progression (it is only conditionally recommended for RA-ILD) 1

Treatment Algorithm for SSc-ILD Flare

1. Assess severity: Determine if this is rapidly progressive ILD requiring urgent intervention versus slower progression
2. If rapidly progressive: Consider pulse IV methylprednisolone for 3 days, then oral prednisone with rapid taper as bridge therapy 2
3. Simultaneously escalate immunosuppression:
   • If not on mycophenolate: Switch to mycophenolate (preferred) 1, 3
   • If already on mycophenolate: Add rituximab OR switch to cyclophosphamide OR add nintedanib 1
4. Taper glucocorticoids rapidly to avoid scleroderma renal crisis 1, 2
5. If continued progression: Consider referral for stem cell transplantation and/or lung transplantation 1, 3

Critical Pitfalls to Avoid

• Never rely on long-term glucocorticoids (>3-6 months) as maintenance therapy in SSc-ILD—this carries a strong recommendation against due to scleroderma renal crisis risk 1, 2
• Do not combine nintedanib with mycophenolate upfront unless there is documented progression on mycophenolate alone 1, 3
• Rule out alternative etiologies (infections, lymphoproliferative disorders) before initiating high-dose steroids 2
• Monitor closely for scleroderma renal crisis when any glucocorticoids are used, especially at doses >15 mg daily prednisone 2, 3

Monitoring During Flare Treatment

• Daily respiratory status assessment and oxygen requirements during acute phase 2
• Monitor for steroid complications: hyperglycemia, hypertension, avascular necrosis 2
• Serial pulmonary function tests every 3-6 months 2
• Appropriate laboratory monitoring based on the specific immunosuppressive agent chosen 1